Type 2 diabetes in latin America: recommendations on the flash glucose monitoring system.

OBJECTIVE: To establish recommendations through the consensus of a Latin American experts panel on the use of the flash glucose monitoring system (fCGM) in people living with type 2 diabetes mellitus (T2DM) regarding the benefits and challenges of using the fCGM. METHODS: An executive committee of experts was created, comprised by a panel of fifteen physicians, including endocrinologists and internal medicine physicians, with expertise in management of adult patients with T2DM. The experts were from various countries: Colombia, Chile, Peru, Mexico, Argentina, and Brazil. The modified Delphi method was used, considering a consensus level of at least 80% of the participants. A seventeen-item instrument was developed to establish recommendations on the use of fCGM in patients with T2DM in Latin American. RESULTS: The number of glucose scans recommended per day with the fCGM for patients managed with oral antidiabetic drugs or basal insulin was a median of 6 scans per day, and for those managed with multiple insulin doses, a median of 10 scans per day was recommended. Additionally, a holistic and individualized management approach was recommended, taking into account new treatment directions and identifying patients who would benefit from the use of the fCGM. CONCLUSION: Continuous use of the fCGM is recommended for people living with T2DM, regardless of their type of treatment. These metrics must be evaluated individually for each patient profile.

Six-Month Glycemic Control with a Hybrid Closed-Loop System in Type 1 Diabetes Patients in a Latin American Country.

The goal of this study was to assess the 6-month effectiveness of hybrid closed loop on glycemic control in type 1 diabetes (T1D) patients in Latin America. An exploratory analysis of data prospectively collected from non-selected consecutive patients with T1D who initiated treatment with the MiniMed™ 670G system in Argentina was conducted. Baseline and follow-up visits at days 7, 28, 90, and 180 were carried out and data were downloaded at each visit. A total of 30 patients (age range 9-57 years, female 63.3%), 73.3% (n = 22) of whom previously used sensor augmented pump-predictive low glucose management (SAP-PLGM), with baseline glycated hemoglobin 7.4% ± 1% were included. Time in range between 70 and 180 mg/dL significantly increased from 65.1% at baseline to 77.3%, 76.2%, 75.7%, and 75.2% at days 7, 28, 90 and 180, respectively. Time above range (>180 mg/dL) significantly decreased from 33% to 22.5% (P < 0.001), while time below range (<70 mg/dL) did not change. Mean glucose levels were reduced from 163.5 mg/dL at baseline to 150.9 mg/dL (P = 0.001) at last visit. The Auto Mode feature was used > 90% of the time. Virtual training was successfully completed with a Net Promoter Score® (NPS®) of 87%. This analysis confirms that MiniMed 670G system use allowed successful achievement of glycemic control within recommended targets in a non-selected Latin American patient population who underwent virtual system training.

A review of flash glucose monitoring in type 2 diabetes.

BACKGROUND: Continuous glucose monitoring systems are increasingly being adopted as an alternative to self-monitoring of blood glucose (SMBG) by persons with diabetes mellitus receiving insulin therapy. MAIN BODY: The FreeStyle Libre flash glucose monitoring system (Abbott Diabetes Care, Witney, United Kingdom) consists of a factory-calibrated sensor worn on the back of the arm which measures glucose levels in the interstitial fluid every minute and stores the reading automatically every 15 min. Swiping the reader device over the sensor retrieves stored data and displays current interstitial glucose levels, a glucose trend arrow, and a graph of glucose readings over the preceding 8 h. In patients with type 2 diabetes (T2D) receiving insulin therapy, pivotal efficacy data were provided by the 6-month REPLACE randomized controlled trial (RCT) and 6-month extension study. Compared to SMBG, the flash system significantly reduced the time spent in hypoglycemia and frequency of hypoglycemic events, although no significant change was observed in glycosylated hemoglobin (HbA1c) levels. Subsequent RCTs and real-world chart review studies have since shown that flash glucose monitoring significantly reduces HbA1c from baseline. Real-world studies in both type 1 diabetes or T2D populations also showed that flash glucose monitoring improved glycemic control. Higher (versus lower) scanning frequency was associated with significantly greater reductions in HbA1c and significant improvements in other measures such as time spent in hypoglycemia, time spent in hyperglycemia, and time in range. Additional benefits associated with flash glucose monitoring versus SMBG include reductions in acute diabetes events, all-cause hospitalizations and hospitalized ketoacidosis episodes; improved well-being and decreased disease burden; and greater treatment satisfaction. CONCLUSION: T2D patients who use flash glucose monitoring might expect to achieve significant improvement in HbA1c and glycemic parameters and several associated benefits.

Monitoreo continuo de glucosa: indicaciones, interpretación de datos y toma de decisiones terapéuticas. Recomendaciones de expertos / Continuous glucose monitoring: indications, data interpretation and making therapeutic decisions. Expert recommendations

Las herramientas para evaluar el grado de control glucémico se modificaron últimamente. La emoglobina glicosilada (HbA1c), parámetro de referencia (gold standard), refleja el control glucémico de los últimos tres meses de manera retrospectiva, sin expresar la variabilidad glucémica. El automonitoreo glucémico capilar (AGC) brinda información inmediata y prospectiva, pero dispone de pocos datos glucémicos para generar promedios y desviaciones estándares representativas. No detecta tendencias y tiene limitaciones para obtener datos nocturnos o durante la actividad física. Es invasivo y muchas veces rechazado. Contrariamente, el monitoreo continuo de glucosa (MCG) mide la glucosa instantáneamente, y muestra sus tendencias y su variabilidad en forma continua, incorporando nuevas métricas de control. Mediante el perfil ambulatorio de glucosa (PAG) se analizan los patrones del control glucémico durante el sueño, los ayunos prolongados, la actividad física y las intercurrencias, expresándolos como curvas con sus desviaciones estándar durante períodos de horas (8 a 24 horas) o días (7, 14, 30 y 90 días). El PAG contiene las siguientes métricas: porcentaje de tiempo en rango TIR (del inglés, time in range), porcentaje de tiempo por encima del rango TAR (del inglés, time above range), porcentaje de tiempo por debajo del rango o hipoglucemia TBR (del inglés, time below range) y coeficiente de variabilidad (%CV). La información continua permite tomar decisiones inmediatas, ya sea con la ingesta de carbohidratos o con la aplicación de insulina. El MCG con terapéuticas insulínicas inyectables (TII) o bomba portable de insulina (BPI) es una herramienta muy útil y complementaria para el tratamiento de la diabetes mellitus tipo 1 (DM1) y la DM2 en la insulinoterapia. Su utilización se asoció con descensos significativos en la HbA1c, disminución de la variabilidad glucémica, reducción de las hipoglucemias totales y nocturnas, y mejoría de la calidad de vida en estos pacientes. Nuestro propósito como grupo de expertos es generar una guía práctica para regular la implementación del MCG.

The tools to assess the degree of glycemic control were modified lately. Glycosylated hemoglobin (HbA1c), the gold standard, reflects the glycemic control of the last 3 months retrospectively, without expressing glycemic variability. Selfblood glucose monitoring (SBGM) provides immediate and prospective information, but has little glycemic data to generate representative averages and standard deviations. It does not detect trends and has limitations to obtain nocturnal data or during physical activity. It is invasive and often rejected. On the contrary, continuous glucose monitoring (CGM), allows to measure glucose instantly, shows your trends and variability continuously, incorporating new control metrics. The ambulatory glucose profile (AGP) analyzes the patterns of glycemic control during sleep, prolonged fasting, physical activity and intercurrences, expressing them as curves with their standard deviations during periods of hours (8 to 24 hours) or days (7, 14, 30 and 90 days). The AGP contains the following metrics: percentage time in range (TIR), percentage time above range mg/dl (TAR), percentage time below range or hypoglycemia (TBR) and coefficient of variation (%CV). CGM with IIT or continuous subcutaneous insulin infusion (CSII), is a very useful and complementary tool for the treatment of DM1 and DM2 in insulin therapy. Its use was associated with significant decreases in HbA1c, decreased glycemic variability, reduction of total and nocturnal hypoglycemia and improvement of the quality of life in these patients. Our aim as a group of experts is to generate a practical guide to regulate the implementation of the CGM.

[Continuous glucose monitoring. Utility and indications]. / Monitoreo continuo de glucosa. Utilidad e indicaciones.

An adequate glycemic control prevents and/or delays the development and/or progression of chronic complications in patients with diabetes mellitus (DM). To achieve this control, it is necessary to adjust insulin doses, in type 1 or insulinized type 2 DM persons, based on traditional capillary glucose self-monitoring, which has limitations to generate an adequate data record, is invasive and has low adherence. In contrast, new continuous glucose monitoring (CGM) systems provide more complete and dynamic information, and better compliance. In these systems, a subcutaneous sensor continuously sends glucose values which are captured and stocked by a receptor module. Real-time models (CGMRT) allow continuous and real-time readings of interstitial glucose, whereas CGM-Flash/EI systems require lector approach to sensor module performing intermittent scanning. CGM shows if glycemic levels are increasing or decreasing and how fast it is happening (tendency). CGM decreases glycosylated hemoglobin between 0.53% and 1.0%, as well as time in hypoglycemia by 38%, increasing the time in range of glucose levels, in patients with high adherence. The objectives of this review are to describe the glycemic homeostasis, to evaluate the accuracy of the CGM to interpret the data adequately and finally, based on the information provided by these novel monitoring systems, to suggest a practical way to be added to the traditional intensive insulin therapy.

[Insulin therapy in special conditions]. / Insulinoterapia en situaciones especiales.

Hyperglycemia during hospitalization is a common condition associated with poor prognosis. To date, insulin is the best strategy to treat hyperglycemia in these patients. An adequate glycemic control is associated with better clinical results. Nevertheless, glycemic goals are still controversial due to the increase of hypoglycemia and other adverse events. Diabetes mellitus is still the main cause of chronic renal failure in our country and its treatment deserves a special analysis considering that insulin pharmacokinetics is altered. Recommendations in this setting are based in expert panel opinions, focusing mainly in intermediate or long acting insulins combined with regular insulin and/or rapid acting analogues. During pregnancy, NPH and regular insulin are safe and effective. It is worth mentioning that the development of new long and rapid acting molecules yielded lower glycemic variability, better post-prandial control and less hypoglycemia. The aim of this study is to provide a review of the proper use of insulin in these special conditions.

Insulinoterapia en situaciones especiales / Insulin therapy in special conditions

La hiperglucemia durante la internación es una condición frecuente que se asocia al aumento de complicaciones y resulta en un mal pronóstico para quienes la padecen. La estrategia para su tratamiento es la insulinoterapia. Un adecuado control glucémico se asocia a mejor evolución y pronóstico. Sin embargo, el nivel adecuado de glucemia se encuentra aún en debate, ya que aquellos ensayos en los cuales se fijaron metas estrictas demostraron incrementar las tasas de hipoglucemia y eventos clínicos adversos. La diabetes mellitus es la principal causa de enfermedad renal crónica en nuestro país. El tratamiento en ese contexto merece un análisis especial, ya que la vida media de la insulina puede resultar prolongada. Las opciones de insulinización en pacientes con enfermedad renal crónica e insuficiencia asociada provienen de recomendaciones de expertos en las cuales se jerarquizan esquemas que utilizan insulina de acción intermedia o prolongada asociadas a insulina regular o análogos de acción rápida. Durante el embarazo, las insulinas NPH y regular han demostrado seguridad y eficacia. Sin embargo, el desarrollo de nuevas moléculas de acción lenta y rápida permitió reducir la variabilidad glucémica, mejorar el control de la glucemia postprandial y reducir la tasa de hipoglucemias. El objetivo del presente trabajo es proporcionar una revisión sobre el adecuado uso de insulina en estas tres situaciones especiales.

Hyperglycemia during hospitalization is a common condition associated with poor prognosis. To date, insulin is the best strategy to treat hyperglycemia in these patients. An adequate glycemic control is associated with better clinical results. Nevertheless, glycemic goals are still controversial due to the increase of hypoglycemia and other adverse events. Diabetes mellitus is still the main cause of chronic renal failure in our country and its treatment deserves a special analysis considering that insulin pharmacokinetics is altered. Recommendations in this setting are based in expert panel opinions, focusing mainly in intermediate or long acting insulins combined with regular insulin and/or rapid acting analogues. During pregnancy, NPH and regular insulin are safe and effective. It is worth mentioning that the development of new long and rapid acting molecules yielded lower glycemic variability, better post-prandial control and less hypoglycemia. The aim of this study is to provide a review of the proper use of insulin in these special conditions.

Bombas de insulina (BI) / Insulin pumps (IP)

En la década pasada, el conocimiento sobre la historia natural y fisiopatogenia de la diabetes tipo 1 tuvo un importante crecimiento, particularmente en relación con predicción, heterogeneidad, patología pancreática y su epidemiología. Las mejoras tecnológicas específicamente en el desarrollo de bombas de insulina y sensores continuos de glucosa ayudan a los pacientes con diabetes tipo 1 en el desafío de la administración de insulina a largo plazo. A pesar de grandes inversiones sobre distintos aspectos de la enfermedad (financiación de proyectos, organizativos, educacionales, etc.) no existe hasta el momento la prevención ni la cura para la diabetes tipo 1, y sumado a esto la calidad sobre el manejo de la enfermedad es muy heterogéneo. Como el control glucémico mejora con un tratamiento intensificado (múltiples inyecciones de insulina), el número y frecuencia de eventos hipoglucémicos tienden a incrementarse. La hipoglucemia es generadora de cuadros de estrés, ansiedad y deterioro de la calidad de vida en los pacientes con diabetes. Una de las razones por las cuales existe gran dificultad de alcanzar los objetivos glucémicos en pacientes con diabetes tipo 1 es la variabilidad en la absorción de la insulina inyectada en forma subcutánea, la que conlleva mayor e impredecible variabilidad en la concentración glucémica y todo esto en general se relaciona con valores elevados de hemoglobina glicosilada e hipoglucemia. La terapia con bomba de insulina se inició hace más de 30 años con el objetivo de mejorar el control en pacientes con diabetes tipo 1. El objetivo de esta revisión es actualizar las herramientas tecnológicas en el tratamiento de la diabetes. (AU)

Over the past decade, knowledge of the pathogenesis and natural history of type 1 diabetes has grown substantially, particularly with regard to disease prediction and heterogeneity, pancreatic pathology, and epidemiology. Technological improvements in insulin pumps and continuous glucose monitors help patients with type 1 diabetes manage the challenge of lifelong insulin administration. Agents that show promise for averting debilitating disease-associated complications have also been identified. However, despite broad organisational, intellectual, and fiscal investments, no means for preventing or curing type 1 diabetes exists, and , globally, the quality of diabetes management remains uneven. As glycemic control improves with intensified insulin regimens, the frequency of hypoglycemia tends to increase. Hypoglycemia is the cause of considerable stress and anxiety, impaired well-being, and poor quality of life in patients with type diabetes. One reason for continued poor glycemic control in patients with type 1 diabetes is the erratic absorption and action of subcutaneously injected insulin, which lead to unpredictable swings in blood glucose concentrations, and those swings, in themselves, are associated with elevated glycated hemoglobin levels and hypoglycemia. Insulinpump therapy, or continuous subcutaneous insulin infusion, was introduced more than 30 years ago as a procedure for improving glycemic control in patients with type 1 diabetes. The primary goal is to perform an up date about the new technological tools in diabetes treatment. (AU)

Endocrine and inflammatory profiles in type 2 diabetic patients with and without major depressive disorder.

BACKGROUND: There is a high prevalence of depression in individuals with type 2 diabetes mellitus. Depressive disorders are associated with increased medical morbidity and mortality in individuals with diabetes. It has been demonstrated that there is a higher prevalence of diabetic complications among individuals with diabetes and depression compared to those without depression. Several biological alterations have been reported in individuals with depressive disorders, particularly abnormal levels of endocrine-inflammatory markers.This study aims to determine the prevalence of major depressive disorder (MDD) in type 2 diabetes patients, the prevalence of cardiovascular events in individuals with and without MDD and to compare the endocrine-inflammatory profile between groups. METHODS: The study was approved by the "Comité de Etica de Protocolos de Investigación del Departamento de Docencia e Investigación del Hospital Italiano de Buenos Aires" with the number "1262" and included only patients who provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki and the Habeas Data law on protection of personal data (Law Nª 25326, Argentina).Type 2 diabetes patients (n = 61) were included and they were classified as having MDD or not according to DSM-IV. Macrovascular disease was obtained from the medical history. Additionally, the intima-media thickness of the common carotid, carotid bifurcations and internal carotid arteries was measured non-invasively by two-dimensional ultrasound imaging. Fasting glucose, fasting lipid profile, inflammatory (CRP, TNF-α) and endocrine (urine free cortisol and saliva cortisol) markers. Student t tests were used to compare means for normally distributed variables and Mann-Whitney test for variables without normal distribution. Relative frequencies were calculated and a chi-square analysis was conducted. Data were expressed as mean ± standard deviation (SD) or median and interquartile range. Multivariable logistic regression was used to determine the relative odds of clinical cardiovascular disease in individuals with compared to those without depression. Differences were considered significant using a two-sided p < 0.05. RESULTS: 21 patients (34%) had MDD and 40 patients (66%) didn't have MDD. Diabetic patients with MDD had significantly higher CRP levels (4.1(1.9-7.6) vs 1.5(0.5-4.4) mg/l; p = 0.02) and 24-hour urine free cortisol (71.4 ± 21.3 vs 59.8 ± 29.3 ug/24 h; p = 0.03). The other metabolic and inflammatory parameters were not statistically different between groups. There was a significantly higher prevalence of cardiovascular events in individuals with MDD: 38% for the depressive group vs 15% for non-depressive group, p = 0.04). Patients with MDD had a 3.5-fold greater odd of having cardiovascular disease. CONCLUSIONS: Diabetic patients with depression are more likely to have cardiovascular events, and different factors can determine this high association.

Índice triglicéridos/HDL-colesterol: en una población de adolescentes sin factores de riesgo cardiovascular

El índice Triglicéridos/HDL- colesterol (TG/HDL) es un recurso de fácil determinación y con buena correlación con el índice HOMA en adultos. Debido a la dificultad que representa la insulinorresistencia (IR) fisiológica de la adolescencia es necesario buscar marcadores de IR independientes de edad, sexo y estadio puberal. El objetivo fue determinar valores de referencia para el índice TG/HDL en una población de adolescentes sin factores de riesgo cardiovascular (CV) Se evaluaron 943 adolescentes, 429 mujeres y 514 varones, entre 11 y 14 años. Se determinaron medidas antropométricas y se calculó índice de masa corporal (IMC). Se realizó extracción de sangre luego de 12 horas de ayuno para determinar glucemia, triglicéridos, HDL. El síndrome metabólico (SM) fue diagnosticado según criterios de NCEP/ ATP III modificado por Cook. Se excluyeron los adolescentes con SM y aquellos con algún carácter del mismo. Ingresaron 562 adolescentes (289 mujeres y 273 hombres). Presentaban un peso de 48.91 ± 6.51kg; IMC de 18.95 ± 1.78, tensión arterial sistólica de 108.12 ± 13.60 mmHg, tensión arterial diastólica 63.82± 9.43 y perímetro de cintura 65.09± 4.54cm; Índice TG/HDL fue de 1.25± 0.43, con un percentilo 95 de 2.05. En el adulto el índice TG/HDL superior a 3 es un marcador de insulinorresistencia. Consideramos que un valor mayor a 2.05 podría ser un buen índice de insulinorresistencia en la adolescencia. El índice TG/HDL tiene la ventaja de ser metodológicamente más sencillo, más económico e independiente de la etapa puberal.

Triglicéridos/HDL- cholesterol ratio: in adolescents without cardiovascular risk factors. Triglicéridos/ HDL- cholesterol ratio (TG / HDL) is an easy resource determination and it has good correlation with the HOMA index in adults. Due to physiological insulin resistance (IR) in adolescence it is necessary to find markers of IR independent of age, sex and pubertal stage. The objective was to identify reference values of TG / HDL ratio in a population of adolescents without cardiovascular risk factors. We evaluated 943 adolescents, 429 females and 514 males between 11 and 14. Anthropometric measures were determined and body mass index was calculated (BMI). Blood was extracted after 12 hours of fasting to determine glucose, triglycerides, HDL. The metabolic syndrome (MS) was diagnosed according to criteria of NCEP / ATP III modified by Cook. We excluded adolescents with MS or any component of it. We evaluated 562 adolescents (289 women and 273 men) with a weight of 48.91 ± 6.51kg, BMI :18.95 ± 1.78, systolic blood pressure of 108.12 ± 13.60 mmHg, diastolic blood pressure: 63.82 ± 9.43 and waist circumference: 65.09 ± 4.54cm. TG / HDL ratio was 1.25 ± 0.43, with a 95 percentile of 2.05. In adults, TG / HDL ratio greater than 3 is a marker of insulin resistance. We believe that a higher value to 2.05 might be a good index of insulin resistance in adolescence. TG / HDL ratio has the advantage of being methodologically simpler, more economical and independent of pubertal stage.

[Triglycerides/HDL-cholesterol ratio: in adolescents without cardiovascular risk factors]. / Indice triglicéridos/HDL-colesterol: en una población de adolescentes sin factores de riesgo cardiovascular.

Triglycerides/HDL-cholesterol ratio (TG/HDL) is an easy resource determination and it has good correlation with the HOMA index in adults. Due to physiological insulin resistance (IR) in adolescence it is necessary to find markers of IR independent of age, sex and pubertal stage. The objective was to identify reference values of TG/HDL ratio in a population of adolescents without cardiovascular risk factors. We evaluated 943 adolescents, 429 females and 514 males between 11 and 14. Anthropometric measures were determined and body mass index was calculated (BMI). Blood was extracted after 12 hours of fasting to determine glucose, triglycerides, HDL. The metabolic syndrome (MS) was diagnosed according to criteria of NCEP/ATP III modified by Cook. We excluded adolescents with MS or any component of it. We evaluated 562 adolescents (289 women and 273 men) with a weight of 48.91 +/- 6.51kg, BMI: 18.95 +/- 1.78, systolic blood pressure of 108.12 +/- 13.60 mmHg, diastolic blood pressure: 63.82 +/- 9.43 and waist circumference: 65.09 +/- 4.54 cm. TG/HDL ratio was 1.25 +/- 0.43, with a 95 percentile of 2.05. In adults, TG/HDL ratio greater than 3 is a marker of insulin resistance. We believe that a higher value to 2.05 might be a good index of insulin resistance in adolescence. TG/HDL ratio has the advantage of being methodologically simpler, more economical and independent of pubertal stage.